Adoptive T cell immunotherapy for treatment of ganciclovir-resistant cytomegalovirus disease in a renal transplant recipient.

Cytomegalovirus (CMV) is a significant cause of morbidity, mortality and graft loss in solid organ transplantation (SOT). Treatment options for ganciclovir-resistant CMV are limited. We describe a case of ganciclovir-resistant CMV disease in a renal transplant recipient manifested by thrombotic microangiopathy-associated glomerulopathy. Adoptive T cell immunotherapy using CMV-specific T cells from a donor bank was used as salvage therapy. This report is a proof-of-concept of the clinical and logistical feasibility of this therapy in SOT recipients.

Retinal drusen in glomerulonephritis with or without immune deposits suggest systemic complement activation in disease pathogenesis.

Retinal drusen are characteristic of macular degeneration and complement activation, but also occur in C3, lupus and IgA nephropathy. This cross-sectional observational study compared drusen counts in different forms of glomerulonephritis. Consecutive individuals with glomerulonephritis attending a general renal or transplant clinic underwent retinal imaging with a non-mydriatic camera. Drusen were counted in deidentified images by trained graders, compared with matched hospital patients, and correlated with clinical features. Eighty-four individuals with glomerulonephritis had a mean drusen count of 10 ± 27 compared with 3 ± 8 in hospital controls (p = 0.007). Fourteen individuals with glomerulonephritis (17%) and 4 hospital controls (4/49, 8%) had increased drusen counts (≥ 10) (p = 0.20). Increased drusen counts ≥ 10 were present in 13 (13/63, 21%)  of those with glomerulonephritis and immune deposits [membranous (n = 8), antiglomerular basement membrane nephritis (n = 6), FSGS (n = 49)], and one of the 21 (5%) with glomerulonephritis without immune deposits [ANCA-associated (n = 15), minimal change disease (n = 6)]. In antibody-mediated glomerulonephritis (n = 14), mean drusen counts were 2 ± 3 in individuals with normal kidney function, 16 ± 41 with impaired function and 5 ± 7 with kidney failure . Mean counts were 24 ± 56 in individuals with glomerular IgG deposits and 1 ± 1 in those without (p = 0.76), and 23 ± 60 with complement deposits and 4 ± 8 in those without. Drusen counts were also less in immunosuppressed individuals (p = 0.049). The demonstration of retinal drusen in some forms of glomerulonephritis is consistent with systemic complement activation, and suggests that treatment targeting the complement pathways is worthwhile.

Changes in urinary and plasma oestrone sulphate concentrations after induction of foetal death in mares at 45 days of gestation.

Foetal death was induced in 10 Standardbred mares at day 45 of gestation by injecting 20 to 45 ml of hypertonic (24% W/V) saline into the conceptus at surgery. Ten mares underwent sham treatment and acted as controls. Blood and urine samples were collected every other day between days 30 and 45 post ovulation and at 0, 3 and 6 h relative to the infusion of saline in the treated mares, or sham treatment in control mares. Blood and urine samples were then collected daily between days 46 and 55 post ovulation. Urine oestrone sulphate (E1S) concentrations, measured by radioimmunoassay, increased between day 34 and day 36 of gestation in treated and control groups. In mares in which foetal death was induced, urine E1S concentrations declined post-operatively and were significantly (p less than .05) lower than controls by day 50. In plasma, E1S concentrations showed a major increase between days 36 and 40 in both groups. This was followed by a rapid decline after treatment in saline-injected mares, so that by day 48 plasma E1S concentrations in treated mares were significantly (P less than .05) lower than the controls. The results show that urinary and plasma E1S concentrations rise rapidly during early pregnancy, and are associated with a viable foetus after day 45 of pregnancy.

Infusion of gonadotrophin-releasing hormone (GnRH) induces ovulation and fertile oestrus in mares during seasonal anoestrus.

In Exp. 1, 30 Standardbred mares in deep seasonal anoestrus were divided into 3 equal groups and treated with 0, 50 (G50) or 100 (G100) ng GnRH kg-1h-1 for 28 days via osmotic minipumps. Ovulation occurred in 0/10, 3/10 and 7/10 mares respectively (P less than 0.05). Plasma GnRH profiles (Days -6, 0, 2, 6, 12, 20, 28 and 34 relative to pump insertion) were dose-dependent (P less than 0.01) and peaked on Day 12 of infusion. Mean daily plasma LH concentrations were biphasic in treated mares that ovulated, with LH peaks occurring around Day 6 and Days 16-20. By contrast, in treated mares that did not ovulate the initial LH rise was followed by a steady decline to the end of the experiment. LH pulse frequency in treated mares increased between Day 0 and Day 21 of the experiment. LH pulse frequency in G100 mares was higher (P less than 0.05) than in G50 and control mares on Day 3, and higher than the controls on Days 7 and 21 of the experiment. There were no significant differences in LH pulse amplitude between the groups on the days studied. In Exp. 2, 27 Standardbred mares in shallow seasonal anoestrus received no treatment (N = 13) or a subcutaneous infusion of GnRH (100 ng kg-1h-1) via osmotic minipump for 28 days (N = 14). Mares were served by a stallion during oestrus. Day of ovulation was earlier in treated than in control mares (18.6 +/- 2 vs 41.9 +/- 6 days; P less than 0.001). Likewise, time of conception was earlier in treated than in control mares (25.2 +/- 6 vs 49.1 +/- 9 days; P less than 0.05). One mare in the control group failed to conceive while one treated mare conceived to an undetected ovulation. The results show that constant GnRH infusion induces ovulation and fertile oestrus in mares during deep and shallow seasonal anoestrus.